| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kitaura, Jiro Ohtsuka, Yoshikazu Okumura, Ko Nakano, Nobuhiro Ogawa, Hideoki Yamazaki, Susumu Honjo, Asuka Maeda, Keiko Hara, Mutsuko Nishiyama, Chiharu Shimizu, Toshiaki |
| Description |
Author Affiliation: Yamazaki S ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Nakano N ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Honjo A ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Hara M ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Maeda K ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Nishiyama C ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Kitaura J ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Ohtsuka Y ( Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Okumura K ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Ogawa H ( Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan); Shimizu T ( Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan) |
| Abstract |
FcεRI, which is composed of , ß, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-ß1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-ß1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family transcriptional factors, is upregulated by TGF-ß/Smad signaling in mouse bone marrow-derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed the transcription of genes encoding FcεRI , FcεRIß, and c-Kit, resulting in a reduction in cell surface FcεRI and c-Kit expression. Additionally, forced expression of Ehf suppressed FcεRI-mediated degranulation and cytokine production. Ehf inhibited the promoter activity of genes encoding FcεRI , FcεRIß, and c-Kit by binding to these gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1 and GATA-2 are positive regulators of FcεRI and c-Kit expression, decreased expression of GATAs may be also involved in the reduction of FcεRI and c-Kit expression. Decreased expression of Stat5 may contribute to the suppression of cytokine production by BMMCs. In part, mast cell response to TGF-ß1 was mimicked by forced expression of Ehf, suggesting that TGF-ß1 suppresses FcεRI and c-Kit expression and suppresses FcεRI-mediated activation through upregulation of Ehf. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
7 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Proto-oncogene Proteins C-kit Biosynthesis Receptors, Ige Immunology Transcription Factors Transforming Growth Factor Beta1 Metabolism Animals Bone Marrow Cells Cell Degranulation Cells, Cultured Cytokines Gata1 Transcription Factor Genetics Gata2 Transcription Factor Immunoglobulin E Mast Cells Mice Mice, Inbred Balb C Promoter Regions, Genetic Rna Interference Rna, Messenger Rna, Small Interfering Stat5 Transcription Factor Signal Transduction Smad Proteins Transcription, Genetic Transcriptional Activation Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
